Peptide class
Peptides that act on melanocortin receptors (MC1R–MC5R) — a family of G protein-coupled receptors mediating pigmentation, sexual function, appetite regulation, and anti-inflammatory signalling.
| Compound | Mechanism | Primary reported use | Profile |
|---|---|---|---|
| PT-141 (Bremelanotide) | Selective MC4R agonist; CNS-mediated sexual arousal | Sexual function research; FDA-approved for female HSDD (Vyleesi) | View profile |
| Melanotan II (MT-II) | Non-selective MC1R/MC3R/MC4R agonist | Tanning/pigmentation research, sexual function, appetite | View profile |
| KPV | MC1R agonist tripeptide (Lys-Pro-Val); anti-inflammatory | Inflammation modulation, gut inflammation, skin research | View profile |
The melanocortin system comprises five receptor subtypes (MC1R–MC5R), all GPCRs signalling primarily through Gs → adenylyl cyclase → cAMP. The endogenous ligands include α-MSH (alpha-melanocyte stimulating hormone) and ACTH (adrenocorticotropic hormone), both derived from the prohormone POMC (pro-opiomelanocortin). Different receptor subtypes have distinct tissue expression patterns and biological functions: MC1R in melanocytes (pigmentation), MC3R and MC4R in the hypothalamus (energy balance, appetite, inflammation), MC4R in the CNS (sexual arousal), and MC5R in exocrine glands.
PT-141 (Bremelanotide) was developed specifically from Melanotan II research with the aim of achieving MC4R selectivity while minimising MC1R activity, thereby producing sexual arousal effects without significant melanogenic (tanning) side effects. Melanotan II is non-selective and activates MC1R (tanning), MC3R (energy homeostasis), and MC4R (sexual function) simultaneously, producing a broader biological response profile. This selectivity difference is the defining pharmacological distinction between the two compounds.
KPV (Lys-Pro-Val) is the C-terminal tripeptide of α-MSH and primarily acts at MC1R, which is expressed not only on melanocytes but also on immune cells including macrophages and dendritic cells. MC1R activation on immune cells suppresses pro-inflammatory cytokine production and NF-κB signalling, making KPV an anti-inflammatory melanocortin peptide distinct from PT-141 or MT-II in its research application. Research has investigated KPV for its potential role in inflammatory bowel disease, skin inflammation, and systemic inflammatory conditions.
The melanocortin system has been studied since the 1950s with the characterisation of MSH and ACTH from pituitary extracts. Melanotan II was developed at the University of Arizona in the 1990s as a tanning agent analogue; from this research emerged PT-141, developed specifically to isolate MC4R agonism for sexual function research. PT-141 (Bremelanotide) received FDA approval in 2019 under the brand name Vyleesi for hypoactive sexual desire disorder (HSDD) in premenopausal women.
Research across the melanocortin class has investigated roles in sexual dysfunction, inflammatory disease, metabolic disorders (MC4R knockout mice develop severe obesity), and skin and hair biology. The anti-inflammatory properties of α-MSH-derived peptides (including KPV) are an active research area in inflammatory bowel disease and dermatology.
PT-141 (Bremelanotide / Vyleesi)
The only FDA-approved compound in this class as of the knowledge cutoff; approved for female HSDD at 1.75 mg intranasal. Research has also investigated it for male erectile dysfunction via the same MC4R-mediated CNS pathway. Unlike PDE5 inhibitors (which act vasodilatorily), PT-141's mechanism is centrally mediated.
Melanotan II (MT-II)
Non-approved compound with no regulatory pathway as of the knowledge cutoff. Produces tanning via MC1R melanocyte activation, sexual effects via MC4R, and pronounced GI side effects (nausea, facial flushing) due to its broad receptor activation. Research interest persists due to its multi-target profile.
KPV
The smallest active melanocortin-derived peptide (tripeptide). Research has investigated KPV for its potential role in reducing intestinal inflammation, wound healing, and dermatological inflammatory conditions. Its small size may permit oral delivery with some biological activity — a property under investigation.